The care of ill patients would be facilitated by continuous monitoring of drug levels, drug effects and biomarkers of the clinical state. An example is monitoring acute organ injury biomarkers, such as the central nervous system (CNS), and effects of anticoagulation drugs during cardiac surgery. Other examples include, but are not limited to, general surgery, trauma, dialysis, sepsis, invasive non-surgical procedures (e.g., cardiac catheterization and ablations), and the like. CNS injury is common after cardiac surgery occurring in at least 36% of neonates, D. B. Andropoulos, et al., Brain Immaturity is Associated with MRI Brain Injury Before and After Neonatal Cardiac Surgery with High-Flow Bypass and Cerebral Oxygenation Monitoring, J Thorac Cardiovasc Surg. 2010 March; 139(3): 543-556, and 1.4-6% of adults have neurologic side effects.
In adults, evidence of post-operative CNS injury is associated with 3-4 fold increased risk of death and major morbidity. Unfortunately, therapies to decrease CNS injury during cardiac surgery are challenged by no objective measures to identify CNS injury as it is occurring. Current clinical assay platforms for measuring biomarkers are typically ELISA based and have a minimum assay time of 30 minutes, which although rapid, significantly limits the therapeutic window for treatment of CNS injury. Development of an electronic biosensor platform for continuous detection of CNS injury biomarkers would fill an important clinical void in cardiac surgery to monitor patients at risk for CNS injury rapidly and easily. The ability of continuous monitoring of blood for brain injury biomarker levels would allow timely intervention, development of new therapies and provide benchmarks for comparing the effectiveness of new therapies.
An example of a brain injury biomarker is glial fibrillary acidic protein (GFAP), an astrocycle specific protein, whose presence in blood is associated with brain injury, and in children with birth asphyxia, C. S. Ennem, et al., Glial Fibrillary Acidic Protein as a Biomarker for Neonatal Hypoxic-Ischemic Encephalopathy Treated with Total Body Cooling, Am J Obstet Gynecol, 205:251, (2011), and extracorporeal membrane oxygenation support. M. M. Bembea, et al., Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation, Pediatr Crit. Care Med 12, 572 (2011). In addition, patients often require significant anticoagulation with drugs like heparin, for example, during cardiac surgery, to prevent blood clotting from exposure to the plastic surfaces if the cardiopulmonary bypass circuit and cannulas. Drugs like heparin require frequent measurements as they are rapidly metabolized, have a narrow therapeutic window and a dosing requirement with wide individual variability. The risks with under (embolic stroke) or over anticoagulation (hemorraghic stroke, subdural hematoma) result in significant mortality and morbidity. The ability to detect brain injury biomarkers and drugs like heparin in real time could dramatically increase their utility, improving patient care, procedure safety and outcomes.